Received: 9/16/2003

Accepted: 2/23/2005

Case Report
Atypical Kawasaki Disease in Two Infants Younger Than 6 Months
H. Dahifar MD*, A. Ghorbani MD**
ABSTRACT
Two infants, a boy and a girl aged 2.5 and 5 months, respectively, were admitted to Tehran's Children Hospital, for fever of unknown origin lasting for about two weeks. The boy presented with abdominal distention, diarrhea, irritability,
pyuria, anemia, leukocytosis, thrombocytosis and raised titer of acute phase reactants. The girl presented with irritability, diarrhea and abdominal distention, Leukocytosis, thrombocytosis, anemia and elevated titer of acute phase reactants. All bacterial cultures and serological tests were negative. Cardiac echocardiography showed coronary artery aneurysm in both patients and confirmed the diagnosis of Kawasaki disease.
These cases showed that atypical Kawasaki disease was often a late diagnosis and therefore should be quickly suspected
in febrile young infants with abnormal inflammatory laboratory results without infection. Echocardiography is an important tool for diagnosis of atypical Kawasaki disease.
Key words: Kawasaki disease, Infant, Coronary artery
JRMS 2005; 10(4): 239-243

awasaki disease (KD) is an illness of

unknown etiology which generally affects children less than 5 years of age1.
It is the leading cause of acquired heart disease
among children in the United States and Japan2. Since the etiology of KD is not known,
the diagnosis is made by persistence of fever
for at least 5 days along with 4 of the following
signs: erythema and swelling of palms and
soles, inflammatory changes of lips and oral
cavity, cervical adenopathy, non-purulent conjunctivitis and polymorphous exanthema3. The
most serious complication of KD is coronary
artery involvement, which has been reported
in about 20% of the patients4.
The term atypical KD describes the condition of children who fail to meet the strict definition for classic KD but have convincing laboratory findings and no other explanations for
their illness5.
The prevalence of such presentation is 710%. KD is uncommon among infants younger
than 3 months 6-8.

In a series of KD patients in Japan, only

1.67% were younger than 3 months 9 but in the
United States, there were no cases of KD in infants younger than 2.25 months of age7.
We report two cases of atypical KD in infants under 6 months who suffered coronary
artery involvement. Here, we try to highlight
atypical presentations, associated features,
confusing and deceptive laboratory findings
and risk factors.

Patient 1:
An Iranian infant boy aged 2.5 months old was
referred to our hospital (Tehrans Children
Hospital) in August 1997, for his fever which
started 15 days earlier besides diarrhea and
irritability. He had already received wide spectrum antibiotics in two separate hospitals. The
patients body temperature was 39.3C. Physical examination revealed only abdominal distention and irritability without dehydration.
The weight was 5,600 grams, blood pressure,
growth criteria and other organs, were normal.

*Assistant Professor, Department of pediatrics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
**Pathobiologist
Correspondence to: Dr. Hossein Dahifar, Shohada Medical Center, Tajrish Sq, Tehran, Iran. E-mail: dr_dahifar@yahoo.com

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Atypical Kawasaki Disease in Very Young Infants

Initial laboratory findings revealed white

blood cell count (WBC) of 22,500/mm3 with a
differential of 58% neutrophils, 40% lymphocytes and 2% monocytes. The platelet count
was 390,000/mm3, erythrocyte sedimentation
rate (ESR) 104 mm/hr, hemoglobin level 8.5
g/dL and CRP++. On repeated blood tests
WBC rose to 34,000/mm3 with a differential of
60% neutrophils, 35% lymphocytes, 5% monocytes, hemoglobin level of 9g/dL. The platelet
count was 1,300,000 /mm3, ESR 135mm/hr,
and CRP ++. Urinalysis showed 20-40 WBC
per high power field with negative culture and
cerebrospinal fluid (CSF) analysis and culture
besides blood culture were normal. Stool
smear and culture was negative, immunoelectrophoresis, Widal and Wright testes were
normal, chest X-ray, barium enema and 24
urine vanylmandelic acid (VMA) were normal.
After 3 days, the patient was sent to the pediatric cardiology unit for echocardiography just
on a clinical suspicion that the illness might be
KD.
The echocardiography revealed a fusifrom
aneurysm of the left coronary artery. Aspirin
was then administered as 100 mg/kg/day for
two weeks and was subsequently reduced to
5mg/kg/day. The desquamation of the fingers
and toes developed one week later and Aspirin
was continued until disappearance of coronary
artery aneurysm and normalization of platelet
count. ESR and CBC became normal about 6
weeks later.

Patient 2:
A 5-month-old Iranian girl was admitted to
our hospital in November 2000, for a 10-dayfever, diarrhea and irritability. She had received ceftriaxon with the diagnosis of urinary
tract infection for 10 days in another hospital
prior to admission, but fever and diarrhea persisted.
On admission the patients body temperature was 39.3C. Physical examination revealed
only abdominal distention and irritability. Her
weight was 5,600 grams with normal growth
pattern. All other organs seemed normal. Initial laboratory findings were hemoglobin level
240

Dahifar et al

8.5g/dL, HCT 35%, WBC 15,400/mm3 with

65% neutrophils, 27% lymphocytes, 4% monocytes and 4% eosinophils. The platelet count
was 832,000/mm3, ESR 125 mm/hr, CRP++,
liver and renal function tests were normal,
stool smear and culture were normal, urinalysis and culture, blood culture, wright and widal agglutination tests were normal. Chest Xray was normal too. Echocardiography was
recommended because of a clinical suspicion
of KD two days after admission.
Echocardiography showed aneurysm of the
right and left coronary arteries. Aspirin as
100mg/kg/day was started for 2 weeks and
was reduced to 5 mg/kg/day thereafter. The
fever stopped and irritability lessened after
three days. Ten days later, desquamation of the
fingers and toes developed. Aspirin was discontinued after normal results of echocardiography, WBC, ESR, CRP and platelet counts
(about 6 weeks later) were reported.

Discussion
As the exact etiology of KD and its specific
laboratory tests remain unknown, the diagnosis of KD basically depends upon the clinical
presentation. The diagnostic criteria for KD are
extremely useful, particularly in preventing
overdiagnosis and overtreatment. Lack of such
criteria may result in unrecognized atypical
features of the illness such as in our two patients in whom significant coronary artery abnormalities developed after only one essential
clinical criterion, Fever of Unknown Origin,
was prolonged. We can prevent severe sequelae with starting appropriate therapy early in
the course of the disease with Aspirin and intravenous gammaglobulin which are extremely useful in reducing the frequency of
coronary artery abnormalities.
In some studies, 28% of infants with KD had
atypical presentation as compared to 7%-10%
in older children 3, 5, 7, 11, 12. The clinical presentation of KD in infants younger than 6 months
was described by some authors 13, 18. Data of
our two patients are presented in table 1.

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Atypical Kawasaki Disease in Very Young Infants

Dahifar et al

Table 1. Presentations of Kawasaki disease in infants younger than 6 months.

Reference

Fever
>5days

Rash

Conjunctivitis

Peripheral
changes

Oral
changes

Lymphadenopathy

WBC>
15000 mm3

ESR
>75/hr

Platelets
>450000
/mm3

13

14

15

16

NS

NS

NS

17

18

Present study

NS= not stated

Japans Kawasaki disease research committee reported associated features in addition to

the essential criteria19, 20. In our patients, diarrhea, abdominal distention and irritability
were associated features. Asai described the
risk factors for prediction of coronary artery
involvement for the first time and formed the
basis for several clinical scoring systems21. Koren renewed those systems22 in a way that they
are now extremely useful in predicting those at
increased risk of coronary artery involvement.
Factors that are most strongly predictive of
coronary disease include male sex, age less
than one year, fever lasting more than 16 days,
cardiomegaly, hemoglobine less than 10g/dL,
WBC greater than 30,000/mm3, ESR higher
than 101mm/hr, positive CRP lasting for more
than 30 days and arrhythmias. In addition, increased platelet counts equal or higher than
900,000/mm3 indicate coronary artery aneurysms in the patient 23, 24. Hirose demonstrated
that coronary dilatation was detected at mean
of 10 days of illness and that the peak frequency of coronary dilation or aneurysms occured within 4 weeks of the onset25. Our patients had several risk factors such as male sex
and WBC>30,000/mm3 in the first patient and
age, fever, hemoglobin less than 10g/dL,
ESR>101mm/hr, positive CRP and platelet
count>900,000/mm3 in both patients.
Jacob Genizi et al, described two boys less
than 6 months of age with coronary abnormali-

ties with four essential criteria of KD except

lymphadenopathy in both infants and
WBC>15,000/mm3, platelets> 450,000/mm3
and ESR>75/hr in one infant. The prevalence
rate of the diagnostic criteria in atypical KD is
variable26. Hsiao et al, found a lower incidence
of strawberry tongue and edema of palms and
soles in patients less that 6 months of age as
compared to older patients27. Also, typical mucosal and lymph node changes were lacking in
those less than 6 months of age28. Tseng et al,
described 48 patients with atypical Kawasaki
disease, of these 35.4% had coronary artery dilation and a longer duration of diagnosis,
higher incidence of atypical presentation,
lower incidence of conjunctivitis, skin rash,
extremity changes and lower C-reactive protein. The predictive value of coronary artery
dilation based on combination of atypical
presentation, duration of diagnosis, and Creactive protein was 81.2%29. Another study
from Netherlands demonstrated atypical Kawasaki in two infants with persistent fever
more than 12 days and lack of classical criteria
with coronary artery dilatation. They believed
that atypical Kawasaki was a late diagnosed
illness30. The clinical presentation of one of
their patients was the same as our patients (irritability, diarrhea).
Many authors believe that diagnosis of
atypical KD is restricted to 3 or 4 of the classical criteria plus coronary artery vasculitis 31, 32.

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Atypical Kawasaki Disease in Very Young Infants

The term atypical or incomplete KD is currently used to describe children who fail to
meet the strict definition for classical KD but
have confirming laboratory findings such as
high ESR, elevated CRP, high neutrophil and
platelet counts and no other explanation for
their illness13. Both of our patients had coronary artery aneurysm and convincing laboratory tests. The previous study demonstrated
85% of infants younger than 6 months of age
with KD developed coronary artery anuerysm26. Nakamura et al, indicated that cardiac
sequelae were much higher in infants, particularly in the first 6 months, than in older children with KD (64% Vs 9%)4, probably owing to
delay in diagnosis. Only 41% of infants
younger than 6 months were treated with
IVIG, of whom only 14% received the therapy
during the first 10 days of their illness 6,7,9,22,33.
This might have contributed to the development of cardiac sequelae.
The diagnosis of KD is based on clinical
presentation and the exclusion of other possible causes. The differential diagnosis of KD in

Dahifar et al

young infants included viral and bacterial infection, drug reaction, and connective tissue
diseases. Our patients did not meet any other
diagnoses, all cultures and serologic tests were
negative, there were no neurologic or articular
signs or skin eruption and mucusal or conjunctival abnormalities.
These cases and other investigations illustrate the fact that atypical KD is often a late
consideration, especially when the symptoms
of the classical form are absent. This condition
should be considered in every infant presenting with long-lasting unexplained fever with
associated features, risk factors of coronary artery involvement and inflammatory tests. Because young infants with KD are at an extremely high risk of developing coronary arterial abnormalities, early diagnosis and appropriate therapy are particularly important. Physicians who evaluate prolonged fever in infants
with or without classical forms of KD should
have high index of suspicion for the possiblity of KD. Echocardiography is the most helpful tool for this diagnosis of the disease.

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